What follows is the comment form Intellicel Biosciences (remember them) regarding the minimal manipulation guidance. I find the simple argument in bold very interesting. The comment period has been extended to 4/29/16.
1.Actual Tissue Manufactured is Lipoaspirate.
The tissue accepted from physicians for processing is lipoaspirate. It is processed using different technologies and in the case of Intellicell, it uses its patented protocol technology with Ultrasonic Cavitation (sound waves) to mechanically break up the blood vessels and microvasculature in the lipoaspirate and then harvest the Stromal Vascular Fraction Cells (SVFCs). The FDA (Agency) has named adipose tissue as the tissue used to manufacture Stromal Vascular Fraction Cells (SVFCs), which is incorrect. Lipoaspirate is the tissue used to manufacture SVFCs. Just as the Agency has named bone marrow aspirate as the tissue use to manufacturer the SVFCs, it should recognize that lipoaspirate is an equivalent tissue.
2.Agencys position is that the tissue used to manufacture SVFCs is adipose, which they define as Structural Tissue.
The Agency has published draft guidance discussing that SVFCs are manufactured from adipose tissue, which they put in the category of structural tissue. The most important fact is that the manufacturing does not use adipose tissue, but instead uses lipoaspirate. The relationship between adipose tissue and lipoaspirate is equivalent to bone marrow tissue and bone marrow aspirate. Bone marrow tissue is structural tissue and bone marrow aspirate is non-structural. This nonstructural bone marrow aspirate is the tissue being used in a mechanical process to isolate the SVFCs. The Intellicell process is based on the same premise and uses non-structural lipoaspirate during a mechanical process to isolate the SVFCs.
The major scientific error here is that the Agency is not recognizing the difference between what is structural and non-structural tissue. Bone marrow and adipose is structural tissue and Bone Marrow Aspirate as well as Lipoaspirate is Non-Structural Tissues.
Bone Marrow is equivalent to Adipose Tissue.
Bone Marrow Aspirate is equivalent to Lipoaspirate.
Bone Marrow & Adipose Tissue are Structural Tissues.
Bone Marrow Aspirate & Lipoaspirate are Non-Structural Tissues.
This is the essence of the misunderstanding by the Agency as to the source of tissue used by for manufacturing.
The second major scientific error made by the Agency is that they state that the major function of adipose tissue is cushioning. The published scientific and medical literature clearly defines the major function of adipose tissue as endocrine and the cushioning aspect as a secondary function. This cushioning aspect is only relevant when the adipose tissue surrounds an organ. There are over 175 scientific peer reviewed references to support this fact. The Agency should use the primary endocrine characteristic of adipose for the purposes of applying the regulatory framework with characteristics for reconstruction, repair, or replacement that relate to its utility.
The cellular components are the cells released during disease and injuries to the bone or joint. They are released for repair, replacement, and healing of the disease. In doing so, they are performing their relevant biological functions. Adipose tissue is never used during this process.
6.FDA CFR 1271.10 (A) criteria to be met:
Under FDAs risk-based HCT/P regulatory framework, which is set forth in 21 CFR Part 1271, certain HCT/Ps are regulated solely under section 361 of the PHS Act and the regulations under 21 CFR Part 1271; no premarket review is required for these HCT/Ps. In 21 CFR 1271.10, the regulations identify the criteria for regulation solely under section 361 of the PHS Act and 21 CFR Part 1271. An HCT/P is regulated solely under section 361 of the PHS Act and 21 CFR Part 1271 if it meets all of the following criteria (21 CFR 1271.10(a)):
1.The HCT/P is minimally manipulated;
2.The HCT/P is intended for homologous use only; as reflected by the labeling, advertising, or other indications of the manufacturer's objective intent;
3.The manufacture of the HCT/P does not involve the combination of the cells or tissues with another article, except for water, crystalloids, or a sterilizing, preserving, or storage agent, provided that the addition of water, crystalloids, or the sterilizing, preserving, or storage agent does not raise new clinical safety concerns with respect to the HCT/P; and
i.The HCT/P does not have a systemic effect and is not dependent upon the metabolic activity of living cells for its primary function; or
ii.The HCT/P has a systemic effect or is dependent upon the metabolic activity of living cells for its primary function, and:
a.Is for autologous use;
b.Is for allogeneic use in a first-degree or second-degree blood relative; or
c.Is for reproductive use.
I would like to address the Agencys comments on their view that the lipoaspirate used in the manufacture of Stromal Vascular Fraction is considered Structural and we feel that scientifically they are in error.